We appreciate your interest in our recent article entitled “Changes in serum magnesium concentration after use of a proton pump inhibitor in patients undergoing percutaneous coronary intervention” [1]. Danziger et al [2] could demonstrate that combined use of proton pump inhibitors (PPIs) and diuretics may increase the risk of hypomagnesemia, although PPI use was not associated with serum magnesium levels among those not using diuretics. A recently published meta-analysis study suggested that the use of PPIs may be associated with hypomagnesemia [3]. However, our study did not show a relationship between PPI use and the occurrence of hypomagnesemia. In addition, a recent study showed that chronic PPI use does not therefore appear to be associated with hypomagnesemia [4].

Inconsistent study results have prevented us from reaching a solid conclusion. In a recent population-based cohort study, PPI use was associated with hypomagnesemia; serum magnesium level was 0.022 mEq/L lower in PPI users compared with nonusers [5]. In the clinical aspect, this lower level of serum magnesium in PPI users may not be significant. But many case reports suggested that PPIs might be associated with hypomagnesemia. Therefore, I think that further studies should focus on the individual sensitivity of hypomagnesemia after PPI use. Drug-induced hypomagnesemia is not unique to PPIs. Other drugs such as gentamicin, calcineurin inhibitors, platinum-based cytostatics, epidermal growth factor receptor–targeting drugs, and diuretics have all been associated with hypomagnesemia. These drugs affect magnesium active transport channels, transient receptor potential melastatin subtype 6, which is responsible for the absorption of magnesium in the kidney and intestine. Until now, it is not known whether PPI therapy may disturb this transport system in the intestine. Further study should reveal whether PPI affects this transport, which can explain the mechanism of PPI-induced hypomagnesemia.

We agree with your opinion that PPI exposure may induce only modest or no significant changes in serum magnesium concentration among patients with normal range of serum magnesium. In addition, I think that it is not necessary to routinely measure magnesium levels after or before PPI use in patients without risk factors, although the clinician should know that PPI use could be associated with hypomagnesemia.